The Unit on Reproductive Endocrinology and Infertility, led by James Segars, investigates underlying causes and effectiveness of treatment for a variety of clinical reproductive disorders. The studies are conducted as an integral facet of the clinical training program in Reproductive Endocrinology and Infertility. The objective is to provide clinician-scientists with a foundation of expertise in basic and clinical research related to reproduction. In the past year, we have begun collaboration with Dr. John Tsibris to investigate the causes of uterine fibroids. Uterine fibroids (also known as leiomyomata), are a benign tumor of the womb that represents a common cause of reproductive disorders. Uterine fibroids afflict up to 22% of African American women and are a significant public health concern; surgeries for fibroids cost over two billion dollars in the United States annually. Studies published this year suggested that fibroids might be distinguished from normal uterine tissue based on abnormal expression of genes involved in growth and growth regulation. Based on these results, fibroids appear to be a feature of disordered differentiation of cells comprising the womb. In a collaboration with the Unit on Reproductive Medicine, led by Dr. Lynnette Nieman, we are participitating in a clinical study to examine the medical treatment and the molecular basis of fibroid disease and expand upon these initial findings. Our basic research studies have continued to explore the relationship of the Brx protooncoprotein to estrogen-mediated responses. Findings this past year have implicated a role for p38 mitogen-activated protein kinases in estrogen action and have further supported a signaling pathway involving cytoplasmic proteins in estrogen action. Current studies are directed to further elucidation of the physiologic role of this signaling pathway in reproduction.